Amino-terminal pro-brain natriuretic peptide predicts ventricular arrhythmogenesis in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators.
Even in high-risk population groups, not all patients have the same risk of sudden cardiac death (SCD). Given the emerging data about the amino-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP) value in heart failure, we planned to evaluate the importance of NT-proBNP levels in predicting the occurrence of malignant arrhythmias in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators (ICDs). Prospective study. Tertiary referral center. Thirty five ambulatory patients with previous myocardial infarction, left ventricular ejection fraction < 35%, and ICDs for primary prevention of SCD according to Multicenter Automatic Defibrillator Implantation Trial I criteria. Venous blood samples for plasma NT-proBNP measurement were obtained after 30 min of supine rest from all patients at the beginning of the study. Patients were evaluated every 2 months, or sooner in cases of device discharges, during a 1-year follow-up period. Data concerning arrhythmias and device therapy were stored at the time of device interrogation on each follow-up visit. During 1-year follow-up, 11 of 35 patients (31.4%) received 18 antiarrhythmic device therapies for ventricular tachyarrhythmia (VT). Patients who experienced such arrhythmias had NT-proBNP levels of 997.27 +/- 335.14 pmol/L (mean +/- SD), whereas those without VT had NT-proBNP levels of 654.87 +/- 237.87 pmol/L (p = 0.001). An NT-proBNP cutoff value of 880 pmol/L had a sensitivity of 73%, a specificity of 88%, a positive predictive value of 80%, and a negative predictive value of 88% for the prediction of occurrence-sustained VT events. To achieve the maximum benefit by ICD therapy, more precise risk stratification is required, even in high-risk, post-myocardial infarction patients. Plasma NT-proBNP levels comprise a promising method that could help in the better identification of a patient group with an even higher risk of sudden death.


parallel secretion of secretory proteins and calcium by the rat parotid gland.
1. The secretion of amylase, deoxyribonuclease, ribonuclease, protein and Ca2+ by the rat parotid gland in vitro was studied. 2. Isoproterenol and carbamoylcholine elicited a parallel discharge of amylase, deoxyribonuclease, ribonuclease and protein over a 40 min time period. 3. The composition of the secretion was independent of the secretogogue used for stimulation. When gland slices from the same animal were stimulated with isoproterenol, adrenaline, phenylephrine or carbamoylcholine, secretory enzymes and protein were secreted in constant proportions. 4. 45Ca injected intraperitoneally 16 h before stimulation with either isoproterenol or carbamoylcholine was released in parallel with amylase and protein. 5. The relative proportions of amylase, ribonuclease, deoxyribonuclease, protein and Ca present in isolated parotid gland secretory granules was identical to that of isoproterenol stimulated gland secretion. 6. It is concluded that the secretory proteins and Ca2+ are discharged in constant proportions by the rat parotid gland regardless of the mode of stimulation or the rate of secretion. The similarity in the composition of gland secretion and granule contents also suggests that enzymes and Ca2+ are released by exocytosis and not by diffusion across the apical plasma membrane.


The cytologist and bacterioses of the vaginal-ectocervical area. Clues, commas and confusion.
To evaluate the role of the cytologist in the diagnosis of bacterial vaginosis, the predominant bacterial patterns seen in 157 Papanicolaou-stained cervical smears were assessed and classified as large bacillus, anaerobic or scanty. A large bacillus pattern was found in 73 smears (46%), an anaerobic pattern in 77 (49%) and scanty bacteria in 7 (5%). Comma-shaped (curved) bacilli were found in 34 smears. The prevalence of clue cells in smears with anaerobic patterns was 73%. Gardnerella vaginalis was cultured from 89% of the cases with anaerobic-type smears containing clue cells and from 88% of those with anaerobic-type smears lacking clue cells. Mobiluncus sp. was cultured from 83% of the cases with anaerobic-type smears showing curved bacilli and 14% of those with anaerobic-type smears lacking curved bacilli. Papanicolaou-stained smears were found to be more sensitive and more specific for identifying clue cells than were wet preparations. A positive association was found between a positive KOH "whiff" test and the presence of curved bacilli on the Papanicolaou-stained smear. The clinical significance of these findings is discussed.


The Association between Iron and Vitamin D Status in Female Elite Athletes.
Vitamin D may influence iron metabolism and erythropoiesis, whereas iron is essential for vitamin D synthesis. We examined whether vitamin D deficiencies (VDD) are associated with reduced iron status and whether progressive iron deficiency (ID) is accompanied by inferior vitamin D status. The study included 219 healthy female (14-34 years old) athletes. VDD was defined as a 25(OH)D concentration < 75 nmol/L. ID was classified based on ferritin, soluble transferrin receptor (sTfR), total iron binding capacity (TIBC) and blood morphology indices. The percentage of ID subjects was higher (32%) in the VDD group than in the 25(OH)D sufficient group (11%) (χ² = 10.6; p = 0.001). The percentage of VDD subjects was higher (75%) in the ID than in the normal iron status group (48%) (χ² = 15.6; p = 0.001). The odds ratios (ORs) for VDD increased from 1.75 (95% CI 1.02-2.99; p = 0.040) to 4.6 (95% CI 1.81-11.65; p = 0.001) with progressing iron deficiency. ID was dependent on VDD in both VDD groups (25(OH)D < 75 and < 50 nmol/L). The ID group had a lower 25(OH)D concentration (p = 0.000). The VDD group had lower ferritin (p = 0.043) and iron (p = 0.004) concentrations and higher values of TIBC (p = 0.016) and sTfR (p = 0.001). The current results confirm the association between vitamin D and iron status in female athletes, although it is difficult to assess exactly which of these nutrients exerts a stronger influence over the other.


Perfluorocarbon-perfused vitrectomy using a transconjunctival 25-gauge system.
To describe the feasibility of perfluorocarbon-perfused vitrectomy (PCPV) using a 25-gauge system in complicated retinal detachment cases. Thirteen nonconsecutive patients with complicated retinal detachment (either tractional secondary to proliferative diabetic retinopathy or rhegmatogenous) who would not normally be selected for 25-gauge vitrectomy were included in the study. Vitrectomy using 25-gauge ports and perfluorocarbon perfusion was performed. Real vitrectomy time, amount of perfluorocarbon liquid (PCL) used, instrument bending, feasibility of surgical maneuvers using an arbitrary scale, and anatomical and visual results were evaluated. Real vitrectomy time ranged from 6.2 minutes to 17.1 minutes (mean, 10.3 minutes). Amount of PCL ranged from 8 mL to 40 mL (mean, 24.38 mL). Instruments never bent even when using a wide-angle sutured contact lens. All desired maneuvers could be performed and were facilitated by PCL. All retinas were reattached, with two cases of mild recurrent vitreous hemorrhage. Visual acuity improved in 76.9% of eyes. PCPV using a 25-gauge system can be performed, even in complicated cases.


Simultaneous fluorometry and phosphorometry of Langendorff perfused rat heart: ex vivo animal studies.
Fluorescence imaging of intrinsic fluorophores of tissue is a powerful method to assess metabolic changes at the cellular and intracellular levels. At the same time, exogenous phosphorescent probes can be used to accurately measure intravascular tissue oxygenation. Heart failure is the leading cause of death in America. A rat heart can potentially model the human heart to study failures or other abnormalities optically. We report simultaneous fluorescence and phosphorescence measurements performed on a rat heart. We have used two different optical systems to acquire fluorescence signals of flavoprotein and nicotinamide adenine dinucleotide--the two intrinsic fluorophores of mitochondria--and the phosphorescence signal of an intravascular oxygen probe to extract intracellular and intravascular metabolism loads, respectively.


Kadsutherin D, a new dibenzocyclooctadiene lignan from Kadsura species.
A new dibenzocyclooctadiene lignan, kadsutherin D (1), together with 12 known lignans, kadsurin (2), heteroclitin C (3), interiotherin C (4), schisanlignone A (5), binankadsurin A (6), angeloyl binankadsurin A (7), gomisin U (8), heteroclitin D (9), interiorin (10), schiarisanrin C (11), heteroclitin G (12) and meso-dihydroguaiaretic acid (13) were isolated from the stems of Kadsura species. Their structures were elucidated by spectroscopic methods including 2D-NMR techniques.


The Development of Ofatumumab, a Fully Human Anti-CD20 Monoclonal Antibody for Practical Use in Relapsing Multiple Sclerosis Treatment.
The importance of B cells in multiple sclerosis (MS) has been demonstrated through the advent of B-cell-depleting anti-CD20 antibody therapies. Ofatumumab is the first fully human anti-CD20 monoclonal antibody (mAb) developed and tested for subcutaneous (SC) self-administration at monthly doses of 20 mg, and has been approved in the US, UK, EU, and other regions and countries worldwide for the treatment of relapsing MS. The development goal of ofatumumab was to obtain a highly efficacious anti-CD20 therapy, with a safety and tolerability profile that allows for self-administration by MS patients at home and a positive benefit-risk balance for use in the broad relapsing MS population. This development goal was enabled by the unique binding site, higher affinity to B cells, and higher potency of ofatumumab compared to previous anti-CD20 mAbs; these properties of ofatumumab facilitate rapid B-cell depletion and maintenance with a low dose at a low injection volume (20 mg/0.4 ml). The high potency in turn enables the selective targeting of B cells that reside in the lymphatic system via subcutaneous (SC) administration. Through a comprehensive dose-finding program in two phase 2 studies (one intravenous and one SC) and model simulations, it was found that safety and tolerability can be further improved, and the risk of systemic injection-related reactions (IRRs) minimized, by avoiding doses ≥ 30 mg, and by reaching initial and rapid B-cell depletion via stepwise weekly administration of ofatumumab at Weeks 0, 1, and 2 (instead of a single high dose). Once near-complete B-cell depletion is reached, it can be maintained by monthly doses of 20 mg/0.4 ml. Indeed, in phase 3 trials (ASCLEPIOS I/II), rapid and sustained near-complete B-cell depletion (largely independent of body weight, race and other factors) was observed with this dosing regimen, which resulted in superior efficacy of ofatumumab versus teriflunomide on relapse rates, disability worsening, neuronal injury (serum neurofilament light chain), and imaging outcomes. Likely due to its fully human nature, ofatumumab has a low immunogenic risk profile-only 2 of 914 patients receiving ofatumumab in ASCLEPIOS I/II developed anti-drug antibodies-and this may also underlie the infrequent IRRs (20% with ofatumumab vs. 15% with the placebo injection in the teriflunomide arm) that were mostly (99.8%) mild to moderate in severity. The overall rates of infections and serious infections in patients treated with ofatumumab were similar to those in patients treated with teriflunomide (51.6% vs. 52.7% and 2.5% vs. 1.8%, respectively). The benefit-risk profile of ofatumumab was favorable compared to teriflunomide in the broad RMS population, and also in the predefined subgroups of both recently diagnosed and/or treatment-naïve patients, as well as previously disease-modifying therapy-treated patients. Interim data from the ongoing extension study (ALITHIOS) have shown that long-term treatment with ofatumumab up to 4 years is well-tolerated in RMS patients, with no new safety risks identified. In parallel to the phase 3 trials in which SC administration was carried out with a pre-filled syringe, an autoinjector pen for more convenient self-administration of the ofatumumab 20 mg dose was developed and is available for use in clinical practice.


Higher Ultrasonic Frequency Liquid Phase Exfoliation Leads to Larger and Monolayer to Few-Layer Flakes of 2D Layered Materials.
Among the most reliable techniques for exfoliation of two-dimensional (2D) layered materials, sonication-assisted liquid-phase exfoliation (LPE) is considered as a cost-effective and straightforward method for preparing graphene and its 2D inorganic counterparts at reasonable sizes and acceptable levels of defects. Although there were rapid advances in this field, the effect and outcome of the sonication frequency are poorly understood and often ignored, resulting in a low exfoliation efficiency. Here, we demonstrate that simple mild bath sonication at a higher frequency and low power positively contributes to the thickness, size, and quality of the final exfoliated products. We show that monolayer graphene flakes can be directly exfoliated from graphite using ethanol as a solvent by increasing the frequency of the bath sonication from 37 to 80 kHz. The statistical analysis shows that ∼77% of the measured graphene flakes have a thickness below three layers with an average lateral size of 13 μm. We demonstrate that this approach works for digenite (Cu9S5) and silver sulfide (Ag2S), thus indicating that this exfoliation technique can be applied to other inorganic 2D materials to obtain high-quality few-layered flakes. This simple and effective method facilitates the formation of monolayer/few layers of graphene and transition metal chalcogenides for a wide range of applications.


Biochemical analysis of acute and chronic wound environments.
The process of wound healing involves a complex interaction between numerous cell types, extracellular matrix molecules, and soluble mediators including growth factors and cytokines. This complex milieu is under active investigation for the purposes of beginning to understand how this environment regulates tissue repair. Quantitation of growth factors, cytokines, and matrix metalloproteinases within surgical wound fluids may help to elucidate this regulatory network, not only in noncomplicated wound healing but also in pathologic lesions such as chronic ulcers.


Sodium Reduction in Processed Foods in Brazil: Analysis of Food Categories and Voluntary Targets from 2011 to 2017.
Non-communicable diseases, including cardiovascular diseases, are responsible for over 70% of deaths in Brazil. Currently, over 25% of Brazilian adults are diagnosed as hypertensive; overall, current dietary sodium intake in Brazil (4700 mg/person) is over twice the international recommendations, and 70-90% of adolescents and adults consume excessive sodium. National sodium reduction strategies consider the main dietary sources of sodium to be added salt to foods, foods consumed outside of the household, and sodium in processed foods. The national voluntary strategy for sodium reduction in priority food categories has been continuously monitored over a 6-year period (2011-2017) and there was a significant 8-34% reduction in the average sodium content of over half food categories. Different food categories have undergone differing reductions in sodium over time, aiding gradual biannual targets to allow industries to develop new technologies and consumers to adapt to foods with less salt. By 2017, most products of all food categories had met the regional targets proposed by the Pan American Health Organization, showing that voluntary sodium reduction strategies can potentially contribute to food reformulation. Nevertheless, regulatory approaches may still be necessary in the future in order to reach all food producers and to allow stronger enforcement to meet more stringent regional targets.


An Outer Membrane-Inspired Polymer Coating Protects and Endows Escherichia coli with Novel Functionalities.
A bio-inspired membrane made of Pluronic L-121 is produced around Escherichia coli thanks to the simple co-extrusion of bacteria and polymer vesicles. The block copolymer-coated bacteria can withstand various harsh shocks, for example, temperature, pressure, osmolarity, and chemical agents. The polymer membrane also makes the bacteria resistant to enzymatic digestion and enables them to degrade toxic compounds, improving their performance as whole-cell biocatalysts. Moreover, the polymer membrane acts as an anchor layer for the surface modification of the bacteria. Being decorated with α-amylase or lysozyme, the cells are endowed with the ability to digest starch or self-predatory bacteria are created. Thus, without any genetic engineering, the phenotype of encapsulated bacteria is changed as they become sturdier and gain novel metabolic functionalities.


Reversible Solid-Solid Conversion of Sulfurized Polyacrylonitrile Cathodes in Lithium-Sulfur Batteries by Weakly Solvating Ether Electrolytes.
Despite carbonate electrolytes exhibiting good stability to sulfurized polyacrylonitrile (SPAN), their chemical incompatibility with lithium (Li) metal anode leads to poor electrochemical performance of Li||SPAN full cells. While the SPAN employs conventional ether electrolytes that suffer from the shuttle effect, leading to rapid capacity fading. Here, we tailor a dilute electrolyte based on a low solvating power ether solvent that is both compatible with SPAN and Li metal. Unlike conventional ether electrolytes, the weakly solvating ether electrolyte enables SPAN to undergo reversibly "solid-solid" conversion. It features an anion-rich solvation structure that allows for the formation of a robust cathode electrolyte interphase on the SPAN, effectively blocking the dissolution of polysulfides into the bulk electrolyte and avoiding the shuttle effect. What's more, the unique electrolyte chemistry endowed Li ions with fast electroplating kinetics and induced high reversibility Li deposition/stripping process from 25 °C to -40 °C. Based on tailored electrolyte, Li||SPAN full cells matched with high loading SPAN cathodes (≈3.6 mAh cm-2 ) and 50 μm Li foil can operate stably over a wide range of temperatures. Additionally, Li||SPAN pouch cell under lean electrolyte and 5 % excess Li conditions can continuously operate stably for over a month.


Effects of severe, uncontrolled hypertension on endothelial activation: soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1 and von Willebrand factor.
The molecular mechanisms whereby severe, uncontrolled hypertension (SHT) is translated into acute vascular target organ dysfunction have not been completely defined. We sought to determine whether SHT is associated with pressure-dependent endothelial activation as assessed by soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and von Willebrand Factor (vWF). We determined sVCAM-1, sICAM-1 and vWF in three groups: (i) untreated patients referred specifically for treatment of SHT [diastolic blood pressure (DBP) > or = 120 mm Hg; n = 24]; (ii) untreated patients with established mild hypertension (MHT; DBP 95-100 mmHg; n = 19); and (iii) normotensive volunteers (DBP < or = 90; n = 16). By analysis of variance, sVCAM-1 (P = 0.002), sICAM-1 (P = 0.02) and vWF (P = 0.009) were greater in SHT and MHT than in normotensives but did not differ between SHT and MHT. We observed a significant positive correlation between blood pressure and soluble activation markers at lower blood pressures (normotensives and MHT considered together) that was not present in SHT. Even mild elevation of blood pressure may be sufficient to activate the expression of adhesion molecules. Mechanisms other than the endothelial expression of adhesion molecules may be important in mediating the accelerated target organ injury produced by SHT in humans. Concentrations of soluble adhesion molecules and vWF may depend more strongly upon factors in the hypertensive microenvironment other than the absolute level of blood pressure.


Diagnosing traumatic arterial injury in the extremities with CT angiography: pearls and pitfalls.
Computed tomographic (CT) angiography is a reliable and convenient imaging modality for diagnosing arterial injuries after blunt and penetrating trauma to the extremities. It is a noninvasive modality that could replace conventional arteriography as the initial diagnostic study for arterial injuries after trauma to the extremities. The technique requires scanning with multidetector helical CT after rapid intravenous injection of iodinated contrast material. The CT angiographic signs of arterial injuries in the extremities are active extravasation of contrast material, pseudoaneurysm formation, abrupt narrowing of an artery, loss of opacification of a segment of artery, and arteriovenous fistula formation. Metallic streak artifact, motion artifact, and inadequate arterial opacification may render a CT angiogram nondiagnostic. Studies have shown the sensitivity of CT angiography to be 90%-95.1% and its specificity 98.7%-100% for detecting arterial injury to the extremities after trauma.


Bacillus cereus NVH 0500/00 Can Adhere to Mucin but Cannot Produce Enterotoxins during Gastrointestinal Simulation.
Adhesion to the intestinal epithelium could constitute an essential mechanism of Bacillus cereus pathogenesis. However, the enterocytes are protected by mucus, a secretion composed mainly of mucin glycoproteins. These may serve as nutrients and sites of adhesion for intestinal bacteria. In this study, the food poisoning bacterium B. cereus NVH 0500/00 was exposed in vitro to gastrointestinal hurdles prior to evaluation of its attachment to mucin microcosms and its ability to produce nonhemolytic enterotoxin (Nhe). The persistence of mucin-adherent B. cereus after simulated gut emptying was determined using a mucin adhesion assay. The stability of Nhe toward bile and pancreatin (intestinal components) in the presence of mucin agar was also investigated. B. cereus could grow and simultaneously adhere to mucin during in vitro ileal incubation, despite the adverse effect of prior exposure to a low pH or intestinal components. The final concentration of B. cereus in the simulated lumen at 8 h of incubation was 6.62 ± 0.87 log CFU ml(-1). At that point, the percentage of adhesion was approximately 6%. No enterotoxin was detected in the ileum, due to either insufficient bacterial concentrations or Nhe degradation. Nevertheless, mucin appears to retain B. cereus and to supply it to the small intestine after simulated gut emptying. Additionally, mucin may play a role in the protection of enterotoxins from degradation by intestinal components.


Effect of melarsoprol treatment on circulating IL-10 and TNF-alpha levels in human African trypanosomiasis.
The pathogenesis of human African trypanosomiasis (HAT) has been the object of considerable research interest but has remained incompletely understood. The importance of cytokines in the pathophysiology of this protozoan infection is now widely recognized, but the full spectrum of cytokines involved has yet to be determined. In the present investigation we compared the plasma concentrations of TNF-alpha and IL-10 in normal African controls and patients suffering from advanced meningocephalic (late-stage) Trypanosomiasis brucei (T.b.) gambiense infections, before and after treatment with the arsenical trypanocide melarsoprol. We found that patients with late-stage T. b. gambiense exhibit chronically elevated circulating levels of both of these cytokines, and that these levels quickly decline following melarsoprol treatment. These findings confirm that TNF-alpha is involved in the immunopathogenesis of late-stage African trypanosomiasis and suggest that IL-10 may also play an important regulatory role in this disease.


Gastric per-oral endoscopic myotomy: Indications, technique, results and comparison with surgical approach.
Gastroparesis is a chronic disease of the stomach that causes a delayed gastric emptying, without the presence of a stenosis. For 30 years the authors identified pylorospasm as one of the most important pathophysiological mechanisms determining gastroparesis. Studies with EndoFLIP, a device that assesses pyloric distensibility, increased the knowledge about pylorospasm. Based on this data, several pyloric-targeted therapies were developed to treat refractory gastroparesis: Surgical pyloroplasty and endoscopic approach, such as pyloric injection of botulinum and pyloric stenting. Notwithstanding, the success of most of these techniques is still not complete. In 2013, the first human gastric per-oral endoscopic myotomy (GPOEM) was performed. It was inspired by the POEM technique, with a similar dissection method, that allows pyloromyotomy. Therapeutical results of GPOEM are similar to surgical approach in term of clinical success, adverse events and post-surgical pain. In the last 8 years GPOEM has gained the attention of the scientific community, as a minimally invasive technique with high rate of clinical success, quickly prevailing as a promising therapy for gastroparesis. Not surprisingly, in referral centers, its technical success rate is 100%. One of the main goals of recent studies is to identify those patients that will respond better to the therapies targeted on pylorus and to choose the better approach for each patient.


Mechanisms of drug resistance and sensitivity concerning novel agents for multiple myeloma.
Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow microenvironment. Novel treatments such as proteasome inhibitors and immunomodulatory agents significantly prolong both progression free survival and overall survival (OS) in patients with MM. However, recent clinical data have indicated that it is difficult to eradicate all MM clones even with the administration of such novel agents. To overcome drug resistance (DR), further investigation of the mechanism underlying DR is required, and strategies to up-regulate, maintain, and restore drug sensitivity will become increasingly important in the clinical setting. The findings from basic research focusing on the microenvironment, genetic abnormalities, and signal transduction disturbances related to MM pathogenesis are excellent strategies for developing new agents. In addition, based on the improved OS over 10 years and the low continuation rate of standard therapy in frail patients, a stratified strategy has the potential to provide total therapy.


Nicotine delivery, tolerability and reduction of smoking urge in smokers following short-term use of one brand of electronic cigarettes.
This randomized, partially single-blinded, 6-period crossover clinical study of adult smokers compared the nicotine pharmacokinetics, impacts on smoking urge and tolerability of various formulations of one brand of e-cigarettes with that of a tobacco cigarette. Five e-cigarettes with different e-liquid formulations containing 1.6 % and 2.4 % nicotine and a conventional tobacco cigarette were randomized among 24 subjects under two exposure sessions consisting of a 30-min controlled and a one-hour ad lib use period to assess plasma nicotine levels, impacts on smoking urge and adverse events. The 30-min controlled use session comprised an intensive use of the e-cigarettes with a total of 50 puffs taken every 30 s for comparison to a single conventional cigarette having a typical machine-measured nicotine yield (~0.8 mg). Ad lib product use conditions provided insight into more naturalistic product use behaviors and their accompanying smoking urge reductions. Adverse events (AEs) were assessed by the Principal Investigator. Significant (p < 0.05) increases in plasma nicotine concentrations occurred within 10 min of controlled e-cigarette use and significant (p < 0.001) reductions from baseline smoking urge were observed within 5 min. E-cigarette and cigarette nicotine plasma levels were comparable for up to one hour of use. After both sessions (90 min), nicotine exposure was the highest for the cigarette, with all e-cigarettes showing 23 % to 53 % lower plasma concentrations. During controlled use, peak reduction in smoking urge for e-cigs occurred later than for the cigarette. After completion of both sessions, significant smoking urge reduction persisted for most of the tested e-cigarettes, albeit at levels lower than that provided by the tobacco cigarette. Nicotine content, vehicle differences, and the presence of menthol did not significantly affect smoking urge reduction by the e-cigarettes. No subjects were discontinued due to AEs. The most frequently reported AEs events included cough, throat irritation, headache, and dizziness. Blood plasma nicotine levels obtained from short-term use of e-cigarettes containing 1.6 % and 2.4 % nicotine were significant, but lower than those of conventional tobacco cigarettes, yet the reduction in craving symptoms were broadly comparable. The types of AEs were consistent with other research studies of longer duration that have reported that use of e-cigarettes by adult smokers is well-tolerated. http://ClinicalTrials.gov identifier: NCT02210754 . Registered 8 August 2014.


Antimicrobial peptides temporins B and L induce formation of tubular lipid protrusions from supported phospholipid bilayers.
The binding of the antimicrobial peptides temporins B and L to supported lipid bilayer (SLB) model membranes composed of phosphatidylcholine and phosphatidylglycerol (4:1, mol/mol) caused the formation of fibrillar protrusions, visible by fluorescent microscopy of both a fluorescent lipid analog and a labeled peptide. Multicolor imaging at low peptide-to-lipid ratios (P/L < approximately 1:5) revealed an initial in-plane segregation of membrane-bound peptide and partial exclusion of lipid from the peptide-enriched areas. Subsequently, at higher P/L numerous flexible lipid fibrils were seen growing from the areas enriched in lipid. The fibrils have diameters <250 nm and lengths of up to approximately 1 mm. Fibril formation reduces the in-plane heterogeneity and results in a relatively even redistribution of bound peptide over the planar bilayer and the fibrils. Physical properties of the lipid fibrils suggest that they have a tubular structure. Our data demonstrate that the peptide-lipid interactions alone can provide a driving force for the spontaneous membrane shape transformations leading to tubule outgrowth and elongation. Further experiments revealed the importance of positive curvature strain in the tubulation process as well as the sufficient positive charge on the peptide (>/=+2). The observed membrane transformations could provide a simplified in vitro model for morphogenesis of intracellular tubular structures and intercellular connections.


Gene Transfer in Rodent Nervous Tissue Following Hindlimb Intramuscular Delivery of Recombinant Adeno-Associated Virus Serotypes AAV2/6, AAV2/8, and AAV2/9.
Recombinant adeno-associated virus (rAAV) vectors have emerged as the safe vehicles of choice for long-term gene transfer in mammalian nervous system. Recombinant adeno-associated virus-mediated localized gene transfer in adult nervous system following direct inoculation, that is, intracerebral or intrathecal, is well documented. However, recombinant adeno-associated virus delivery in defined neuronal populations in adult animals using less-invasive methods as well as avoiding ectopic gene expression following systemic inoculation remain challenging. Harnessing the capability of some recombinant adeno-associated virus serotypes for retrograde transduction may potentially address such limitations (Note: The term retrograde transduction in this manuscript refers to the uptake of injected recombinant adeno-associated virus particles at nerve terminals, retrograde transport, and subsequent transduction of nerve cell soma). In some studies, recombinant adeno-associated virus serotypes 2/6, 2/8, and 2/9 have been shown to exhibit transduction of connected neuroanatomical tracts in adult animals following lower limb intramuscular recombinant adeno-associated virus delivery in a pattern suggestive of retrograde transduction. However, an extensive side-by-side comparison of these serotypes following intramuscular delivery regarding tissue viral load, and the effect of promoter on transgene expression, has not been performed. Hence, we delivered recombinant adeno-associated virus serotypes 2/6, 2/8, or 2/9 encoding enhanced green fluorescent protein (eGFP), under the control of either cytomegalovirus (CMV) or human synapsin (hSyn) promoter, via a single unilateral hindlimb intramuscular injection in the bicep femoris of adult C57BL/6J mice. Four weeks post injection, we quantified viral load and transgene (enhanced green fluorescent protein) expression in muscle and related nervous tissues. Our data show that the select recombinant adeno-associated virus serotypes transduce sciatic nerve and groups of neurons in the dorsal root ganglia on the injected side, indicating that the intramuscular recombinant adeno-associated virus delivery is useful for achieving gene transfer in local neuroanatomical tracts. We also observed sparse recombinant adeno-associated virus viral delivery or eGFP transduction in lumbar spinal cord and a noticeable lack thereof in brain. Therefore, further improvements in recombinant adeno-associated virus design are warranted to achieve efficient widespread retrograde transduction following intramuscular and possibly other peripheral routes of delivery.


High-Risk Histopathology Features in Primary and Secondary Enucleated International Intraocular Retinoblastoma Classification Group D Eyes.
To evaluate the rate and identify the risk factors for high-risk histopathologic features in group D retinoblastoma eyes enucleated as primary or secondary treatment. Retrospective analysis. A total of 64 enucleated group D eyes (62 patients), of which 40 (40 patients) were primary and 24 (22 patients) were secondary to other treatments. Clinicopathologic correlation of consecutive group D eyes enucleated from 2002 to 2014. High-risk histopathologic features were defined as the presence of anterior chamber seeds, iris infiltration, ciliary body/muscle infiltration, massive (≥3 mm) choroidal invasion, retrolaminar optic nerve invasion, or combined non-massive choroidal and prelaminar/laminar optic nerve invasion. High-risk histopathologic features, metastasis, and death. Of the 64 group D eyes, 37 (58%) were classified as cT2bN0M0H0, 24 (38%) were classified as cT2bN0M0H1, and 3 (5%) were classified as cT2aN0M0H1, according to the 8th edition cTNMH Retinoblastoma Staging. High-risk histopathologic features were detected in 10 eyes (16%) in the entire cohort, 5 eyes (13%) of the primary enucleated group (pT3aNxM0, n = 2 and pT3bNxM0, n = 3, 8th edition pTNM), and 5 eyes (21%) of the secondary enucleated group (pT2bNxM0, n = 2, pT3aNxM0, n = 2 and pT3cNxM0, n = 1). Absence of vitreous seeds at presentation was the only predictive factor found for high-risk histopathologic features in the primary enucleation group (P = 0.042), whereas none were found in the secondary group (P ≥ 0.179). Invasion of the anterior structures (anterior chamber, iris, ciliary body/muscle) was detected significantly more after secondary enucleation (P = 0.048). All patients with high-risk histopathologic features were treated with adjuvant chemotherapy, and no metastases were recorded in a median follow-up time of 73.2 months (mean, 71.5; range, 13.7-153.0). The choice of primary treatment for group D retinoblastoma should be carefully weighed, because according to this study, 13% of eyes harbor high-risk histopathologic features at presentation, with the absence of vitreous seeds being a potential risk factor. It is of special importance in group D eyes being considered for nonsystemic treatment, such as primary intraophthalmic artery chemotherapy. Secondary enucleated group D eyes with high-risk histopathologic features more commonly involved anterior structures, warranting meticulous clinical and histologic examinations for this subset of patients.


Crystallization and preliminary X-ray diffraction analysis of crystals of Thermoascus aurantiacus xylanase.
Crystals suitable for high resolution X-ray diffraction analysis have been grown of the 29,774-Da protein, xylanase (1,-4-beta-xylan xylanohydrolase EC 18.104.22.168) from the thermophilic fungus Thermoascus aurantiacus. This protein, an endoxylanase demonstrates the hydrolysis of beta-(1-4)-D-xylose linkage in xylans and crystallizes as monoclinic pinacoids in the presence of ammonium sulphate buffered at pH 6.5, and also with neutral polyethylene glycol 6000. The crystals belong to space group P2(1) and have cell dimensions, a = 41.2 A, b = 67.76 A, c = 51.8 A; beta = 113.2 degrees.


Surgeon Volume Correlates with Reduced Mortality and Improved Quality in the Surgical Management of Diverticulitis.
Volume has been shown to be an important determinant of quality and cost outcomes. We performed a retrospective study of patients who underwent surgery for diverticulitis using the University HealthSystem Consortium database from 2008–2012. Outcomes evaluated included minimally invasive approach, stoma creation, intensive-care admission, post-operative complications, length of stay, and total direct hospital costs by surgeon volume. Surgeon volume was categorized into four categories by mean annual volumes: very-high (VHVS) (>31), high (HVS) (13–31), medium (MVS) (6–12), and low (LVS) (≤5). A total of 19,212 patients with a mean age of 59 years, 54 % female makeup, and 55 % rate of private insurance were included. Similar to the unadjusted analysis, multivariable analysis revealed decreasing odds of stoma creation, complications, ICU admission, reoperation, readmission, and inpatient mortality with increasing surgeon volume. Additionally, compared with LVS, a higher surgeon volume was associated with higher rates of the minimally invasive approach. Median length of stay and costs were also notably lower with increasing surgeon volume. Quality and the use of minimally invasive technique are tightly associated with surgeon volume. Further studies are necessary to validate the direct association of volume with outcomes in surgery for diverticulitis.


Citizen's Charter in a primary health-care setting of Nepal: An accountability tool or a "mere wall poster"?
Despite some empirical findings on the usefulness of citizen's charters on awareness of rights and services, there is a dearth of literature about charter implementation and impact on health service delivery in low-income settings. To gauge the level of awareness of the Charter within Nepal's primary health-care (PHC) system, perceived impact and factors affecting Charter implementation. Using a case study design, a quantitative survey was administered to 400 participants from 22 of 39 PHC facilities in the Dang District to gauge awareness of the Charter. Additionally, qualitative interviews with 39 key informants were conducted to explore the perceived impact of the Charter and factors affecting its implementation. Few service users (15%) were aware of the existence of the Charter. Among these, a greater proportion were literate, and there were also differences according to ethnicity and occupational group. The Charter was usually not properly displayed and had been implemented with no prior public consultation. It contained information that provided awareness of health facility services, particularly the more educated public, but had limited potential for increasing transparency and holding service providers accountable to citizens. Proper display, consultation with stakeholders, orientation or training and educational factors, follow-up and monitoring, and provision of sanctions were all lacking, negatively influencing the implementation of the Charter. Poor implementation and low public awareness of the Charter limit its usefulness. Provision of sanctions and consultation with citizens in Charter development are needed to expand the scope of Charters from information brochures to tools for accountability.


Identification of natural killer (NK) cells in lesions of human cutaneous graft-versus-host disease: expression of a novel NK-associated surface antigen (Kp43) in mononuclear infiltrates.
We performed an immunohistochemical analysis of skin biopsies from 13 allogeneic bone marrow transplant (BMT) recipients, undergoing either acute graft-versus-host-disease (aGVHD, n = 8) or chronic GVHD (cGVHD, n = 5). A panel of different monoclonal antibodies (MoAb) was employed including anti-CD2, -CD3, -CD4, -CD8, -CD11b, -CD16, -CD56, and -CD57, as well as a recently described reagent (HP-3B1) specific for a novel natural killer (NK)-associated cell-surface antigen (Kp43). Our data indicate that in aGVHD lesions the proportions of CD2+ cells often exceeded those detected with anti-CD3 MoAb. Double labeling confirmed the presence of CD2+ CD3- lymphocytes and suggested the coexpression in some cells of CD2 and CD11b. When MoAb specific for non-lineage-restricted NK-associated markers were employed, anti-CD56 and -CD57 occasionally stained variable numbers of lymphocytes (means = 14.6% of mononuclear cells in 0.05 mm2, range less than 1-48% and means = 10.3%, range 2-25%, respectively), whereas no CD16+ lymphocytes were observed. In contrast, most samples consistently displayed substantial proportions of Kp43+ cells (means = 32.8%, range 12-63%), which appeared CD3- and were mainly located at the dermoepidermal junction. On the other hand, sections from most (four of five) cGVHD lichenoid lesions analyzed displayed lower proportions of Kp43+ and CD56+ cells. Our data point out the interest of the anti-Kp43 MoAb to identify NK cells in aGVHD lesions, suggesting their pathogenetic participation.


Healing Effect of Controlled Anti-Electromigration on Conventional and High-Tc Superconducting Nanowires.
The electromigration process has the potential capability to move atoms one by one when properly controlled. It is therefore an appealing tool to tune the cross section of monoatomic compounds with ultimate resolution or, in the case of polyatomic compounds, to change the stoichiometry with the same atomic precision. As demonstrated here, a combination of electromigration and anti-electromigration can be used to reversibly displace atoms with a high degree of control. This enables a fine adjustment of the superconducting properties of Al weak links, whereas in Nb the diffusion of atoms leads to a more irreversible process. In a superconductor with a complex unit cell (La2-x Cex CuO4 ), the electromigration process acts selectively on the oxygen atoms with no apparent modification of the structure. This allows to adjust the doping of this compound and switch from a superconducting to an insulating state in a nearly reversible fashion. In addition, the conditions needed to replace feedback controlled electromigration by a simpler technique of electropulsing are discussed. These findings have a direct practical application as a method to explore the dependence of the characteristic parameters on the exact oxygen content and pave the way for a reversible control of local properties of nanowires.


P-glycoprotein expression as a predictor of the outcome of therapy for neuroblastoma.
Multidrug resistance in chemotherapy for cancer is characterized by increased genetic expression of P-glycoprotein, which acts as an ATP-dependent drug-efflux pump. To determine whether P-glycoprotein levels are of prognostic value in such cases, we measured these levels immunohistochemically in a retrospective study of sequential tumor samples from 67 children with neuroblastoma. P-glycoprotein was not detected in pretreatment samples from either of the 2 patients with Stage I disease, any of the 21 with Stage II disease, or any of the 8 with Stage IVS disease, but it was detected in the samples from 1 of the 17 patients with Stage III disease (6 percent) and 12 of the 19 with Stage IV disease (63 percent). Of the 44 patients with nonlocalized neuroblastoma (Stage III, IVS, or IV), 26 of the 31 who were negative for P-glycoprotein had a complete response to primary treatment, as compared with 6 of the 13 who were positive for P-glycoprotein (84 percent vs. 46 percent, P = 0.0232 by Fisher's exact test). Log-rank analysis of outcome, with simultaneous stratification according to tumor stage and age, showed that the group that was negative for P-glycoprotein had significantly longer relapse-free survival (P = 0.0011) and overall survival (P = 0.0373) than the group that was positive. Expression of P-glycoprotein before treatment may predict the success or failure of therapy for nonlocalized neuroblastoma. Neuroblastoma may be a promising tumor to treat with anticancer drug therapy combined with a chemosensitizing agent capable of reversing P-glycoprotein-mediated multidrug resistance.


Aerosol-Printed MoS2 Ink as a High Sensitivity Humidity Sensor.
Molybdenum disulfide (MoS2) is attractive for use in next-generation nanoelectronic devices and exhibits great potential for humidity sensing applications. Herein, MoS2 ink was successfully prepared via a simple exfoliation method by sonication. The structural and surface morphology of a deposited ink film was analyzed by scanning electron microscopy (SEM), Raman spectroscopy, and atomic force microscopy (AFM). The aerosol-printed MoS2 ink sensor has high sensitivity, with a conductivity increase by 6 orders of magnitude upon relative humidity increase from 10 to 95% at room temperature. The sensor also has fast response/recovery times and excellent repeatability. Possible mechanisms for the water-induced conductivity increase are discussed. An analytical model that encompasses two ionic conduction regimes, with a percolation transition to an insulating state below a low humidity threshold, describes the sensor response successfully. In conclusion, our work provides a low-cost and straightforward strategy for fabricating a high-performance humidity sensor and fundamental insights into the sensing mechanism.


[Lycopene for the treatment of chronic prostatitis / chronic pelvic pain syndrome: Effect and mechanism based on network pharmacology and molecular docking].
To explore the action mechanisms of lycopene in the treatment of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) based on network pharmacology and molecular docking. We obtained the drug targets of lycopene from the databases TCMSP and PharmMapper, the therapeutic targets of CP/CPPS from OMIM, Disgenet and Genecards, and the common targets of lycopene and CP/CPPS with the Venny software. We constructed a protein-protein interaction (PPI) network of lycopene acting on CP/CPPS using the STRING database, screened the core targets with the Cytoscape software, followed by GO functional analysis and KEGG pathway analysis with the R software and molecular docking of lycopene and the core targets using AutoDock Tools, Vina and Pymol. A total of 187 drug targets, 1 557 disease targets and 46 common targets were screened out. PPI network analysis showed that ALB, IGF1, EGFR, SRC, CASP3 and ESR1 were the core targets of lycopene in the treatment of CP/CPPS. GO functional analysis showed the common targets to be involved in the reproductive structure development, extrinsic apoptotic signaling pathway, and response to reactive oxygen species. KEGG pathway analysis indicated the association of Ras, PI3K-Akt, Rap1, FoxO and MAPK signaling pathways with the mechanism of lycopene acting on CP/CPPS. Molecular docking exhibited a great affinity of lycopene to all the core targets. This study revealed the potential targets and signaling pathways of lycopene in the treatment of CP/CPPS and its action mechanisms from the perspective of network pharmacology and molecular docking, which has provided some reference for future studies.


Introduction of a cis-prolyl mimic in position 7 of the peptide hormone oxytocin does not result in antagonistic activity.
New insights into the structure-activity relationship of the peptide hormone oxytocin are presented. Incorporation of the novel cis-prolyl mimic 2,2-dimethyl-1,3-thiazolidine-4-carboxylic acid (pseudoproline, PsiPro) at position 7 of the hormone yielded the analogue [Cys(Psi(Me,Me)pro)]7oxytocin (1) that showed a 92-95% induction of the cis peptide bond conformation between Cys6 and PsiPro7, as determined by one- and two-dimensional NMR spectra in water and in DMSO-d6. The impact of the dimethyl moiety regarding conformation and bioactivity was investigated by the synthesis of the corresponding dihydro compound, [Cys(Psi(H,H)pro)]7oxytocin (2). Biological tests of the uterotonic activity, the pressor activity, and the binding affinity to the rat and human oxytocin receptors were carried out. As a most significant result, no antagonistic activities were found for both the cis-constrained analogue 1 and analogue 2, suggesting that a cis conformation between residues 6 and 7 of the molecule does not result in antagonistic activity. However, the about 10-fold reduction in agonistic activity of 1 as compared to oxytocin is consistent with the reduction of the trans conformation from 90% for oxytocin to 5-8% for compound 1. Compound 1 retained a high binding affinity for the oxytocin receptor, with K(i) values of 8.0 and 1.9 nM for the rat and the human receptor, respectively. The correlation between the biological activities and the cis contents obtained from NMR analysis for compounds 1, 2, and oxytocin leads to the hypothesis that a cis/trans conformational change plays an important role in oxytocin receptor binding and activation.


Surgical treatment of "tuberculoma". A follow-up examination of patients with pulmonary tuberculosis resected on suspicion of tumour.
On suspicion of tumour, thoracotomy was performed in 91 patients, who proved to have pulmonary tuberculosis. Short-term antituberculous chemotherapy was given pre-operatively in 66 cases. The 89 surviving patients received antituberculous chemotherapy after operation, and were examined one year after its termination. No signs of dissemination or other tuberculous manifestations were found, whether pre-operative therapy had been given or not.


Surrogate and clinical endpoints for studies in peripheral artery occlusive disease: Are statistics the brakes?
The aim of this review is to present the available clinical and surrogate endpoints that may be used in future studies performed in patients with peripheral artery occlusive disease (PAOD). Importantly, we describe statistical limitations of the most commonly used endpoints and offer some guidance with respect to study design for a given sample size. The proposed endpoints may be used in studies using surgical or interventional revascularization and/or drug treatments. Considering recently published study endpoints and designs, the usefulness of these endpoints for reimbursement is evaluated. Based on these potential study endpoints and patient sample size estimates with different non-inferiority or tests for difference hypotheses, a rating relative to their corresponding reimbursement values is attempted. As regards the benefit for the patients and for the payers, walking distance and the ankle brachial index (ABI) are the most feasible endpoints in a relatively small study samples given that other non-vascular impact factors can be controlled. Angiographic endpoints such as minimal lumen diameter (MLD) do not seem useful from a reimbursement standpoint despite their intuitiveness. Other surrogate endpoints, such as transcutaneous oxygen tension measurements, have yet to be established as useful endpoints in reasonably sized studies with patients with critical limb ischemia (CLI). From a reimbursement standpoint, WD and ABI are effective endpoints for a moderate study sample size given that non-vascular confounding factors can be controlled.


Effectiveness of falls prevention interventions for older adults newly discharged from hospital: a systematic review protocol.
The objective of this review is to synthesize the best available evidence on the effectiveness of falls prevention interventions provided just prior or immediately after discharge from hospital on falls rates and falls injuries among older adults living in the community in the first 6 months after discharge from hospital.


One-Week Suicide Risk Prediction Using Real-Time Smartphone Monitoring: Prospective Cohort Study.
Suicide is a major global public health issue that is becoming increasingly common despite preventive efforts. Though current methods for predicting suicide risk are not sufficiently accurate, technological advances provide invaluable tools with which we may evolve toward a personalized, predictive approach. We aim to predict the short-term (1-week) risk of suicide by identifying changes in behavioral patterns characterized through real-time smartphone monitoring in a cohort of patients with suicidal ideation. We recruited 225 patients between February 2018 and March 2020 with a history of suicidal thoughts and behavior as part of the multicenter SmartCrisis study. Throughout 6 months of follow-up, we collected information on the risk of suicide or mental health crises. All participants underwent voluntary passive monitoring using data generated by their own smartphones, including distance walked and steps taken, time spent at home, and app usage. The algorithm constructs daily activity profiles for each patient according to these data and detects changes in the distribution of these profiles over time. Such changes are considered critical periods, and their relationship with suicide-risk events was tested. During follow-up, 18 (8%) participants attempted suicide, and 14 (6.2%) presented to the emergency department for psychiatric care. The behavioral changes identified by the algorithm predicted suicide risk in a time frame of 1 week with an area under the curve of 0.78, indicating good accuracy. We describe an innovative method to identify mental health crises based on passively collected information from patients' smartphones. This technology could be applied to homogeneous groups of patients to identify different types of crises.


Regulatory elements responsible for inducible expression of the granulocyte colony-stimulating factor gene in macrophages.
Granulocyte colony-stimulating factor (G-CSF) plays an essential role in granulopoiesis during bacterial infection. Macrophages produce G-CSF in response to bacterial endotoxins such as lipopolysaccharide (LPS). To elucidate the mechanism of the induction of G-CSF gene in macrophages or macrophage-monocytes, we have examined regulatory cis elements in the promoter of mouse G-CSF gene. Analyses of linker-scanning and internal deletion mutants of the G-CSF promoter by the chloramphenicol acetyltransferase assay have indicated that at least three regulatory elements are indispensable for the LPS-induced expression of the G-CSF gene in macrophages. When one of the three elements was reiterated and placed upstream of the TATA box of the G-CSF promoter, it mediated inducibility as a tissue-specific and orientation-independent enhancer. Although this element contains a conserved NF-kappa B-like binding site, the gel retardation assay and DNA footprint analysis with nuclear extracts from macrophage cell lines demonstrated that nuclear proteins bind to the DNA sequence downstream of the NF-kappa B-like element, but not to the conserved element itself. The DNA sequence of the binding site was found to have some similarities to the LPS-responsive element which was recently identified in the promoter of the mouse class II major histocompatibility gene.


Clinical value of 12-lead electrocardiography to predict the long-term prognosis of GISSI-1 patients.
We evaluated the prognostic relevance of the extent of myocardial injury, as measured by a standard electrocardiographic (ECG) method, on the patients' long-term prognosis, its time dependence and its relation to fibrinolytic therapy efficacy. Many clinical and instrumental variables influence the short- and long-term prognoses of patients with acute myocardial infarction (MI). The extent of myocardial injury is relevant to predict both the short-term prognosis and the benefit of fibrinolytic treatment. In 8,731 patients with MI enrolled in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto (GISSI-1) study, the number of ECG leads with ST-segment elevation was used to define the extent of myocardial injury and four different severity groups: A, B, C and D, with ST-segment elevation in two or three leads, four or five leads, six or seven leads and more than eight leads, respectively. At 10 years, the mortality rates were 36.6%, 41.0%, 47.9% and 51.2% in groups A, B, C and D, respectively. At 30 days, according to the extent of myocardial injury, the relative risk (RR) of death was significantly higher for groups B, C and D, compared with group A (RR 1.19 and 95% confidence interval [CI] 1.06 to 1.34 for group B; RR 1.54 and 95% CI 1.31 to 1.80 for group C; RR 2.01 and 95% CI 1.69 to 2.39 for group D). At one-year follow-up, the RR of death remained higher for groups C and D, whereas, subsequently, the extent of myocardial injury did not influence the RR of death. At 10 years, the differences in fibrinolytic treatment benefit between the four groups were similar to those at hospital discharge. At 10 years, the survival rate appears to be related to the extent of myocardial injury, as evaluated by ST-segment elevation on the admission ECG.


Biased percolation on scale-free networks.
Biased (degree-dependent) percolation was recently shown to provide strategies for turning robust networks fragile and vice versa. Here, we present more detailed results for biased edge percolation on scale-free networks. We assume a network in which the probability for an edge between nodes i and j to be retained is proportional to (k(i)k(j)(-alpha) with k(i) and k(j) the degrees of the nodes. We discuss two methods of network reconstruction, sequential and simultaneous, and investigate their properties by analytical and numerical means. The system is examined away from the percolation transition, where the size of the giant cluster is obtained, and close to the transition, where nonuniversal critical exponents are extracted using the generating-functions method. The theory is found to agree quite well with simulations. By presenting an extension of the Fortuin-Kasteleyn construction, we find that biased percolation is well-described by the q-->1 limit of the q -state Potts model with inhomogeneous couplings.


[The role of apolipoprotein M and sphingosine 1-phosphate axis in the prevention of atherosclerosis].
Previous studies showed that plasma levels of high-density lipoprotein (HDL) cholesterol are inversely related to risk of cardiovascular diseases. However, in the last few decades it became obvious that beyond its plasma level, HDL structure and function have a critical role in its anti-atherogenic efficacy. Apolipoprotein M (ApoM) is an HDL-associated plasma protein affecting HDL metabolism and exhibits various anti-atherosclerotic functions, such as protection against oxidation and regulation of cholesterol efflux. Sphingosine 1-phosphate (S1P) is a potent sphingolipid mediator that regulates numerous cellular responses including cell differentiation and migration, apoptosis and vascular inflammation. The majority of S1P is associated to ApoM containing HDL particles. Therefore, ApoM and S1P content of HDL have an impact on the atherosclerotic process. Moreover, HDL-ApoM and S1P content can be altered in several pathologic conditions such as coronary artery disease. This review covers the currently available data on the contribution of ApoM and S1P to HDL function in health and cardiovascular diseases. Orv Hetil. 2018; 159(5): 168-175.


Comparative study of craniofacial morphology and bite force in Fijians and Japanese.
An anthropological survey was conducted in Fiji in 1994 and 1995 to study dental arch form, craniofacial morphology, and bite force of Fijians. Measurements were obtained from dental casts, cephalograms, and thin pressure-sensitive sheets (Dental Prescale®) for bite force analysis. Results were compared with those of Japanese. In every direction, the size of the dental arch in Fijians was larger than in Japanese. Fijians displayed longer palates, longer mandibles, and bimaxillary protrusion. There was no significant difference in upper and lower facial heights. FH to lower incisor angle in Fijians was significantly larger than in Japanese. Fijians were characterized by a small palatal plane angle, occlusal plane angle and mandibular plane angle, and were thus brachyfacial. The Japanese tended to be more dolichofacial. The distances from the Cd line to the pterygoid muscles, masseter muscles, and teeth in Fijians were significantly longer than in Japanese. Occlusal contact areas of Fijians were also greater than those of Japanese. The results indicate that the masticatory muscles and craniofacial morphologies supporting them would be better integrated in Fijians than in Japanese. Am. J. Hum. Biol. 10:63-72, 1998. © 1998 Wiley-Liss, Inc.


Predictors of mortality from fires in young children.
In the United States in 1994, fires claimed 3.75 lives per 100 000 child years and accounted for 17.3% of all injury deaths in children <5 years of age. To conduct a historical cohort study that uses maternal demographic characteristics to identify young children at high risk of fire-related deaths, thus defining appropriate targets for prevention programs. The cohort consisted of children born to mothers who resided in the state of Tennessee between 1980 and 1995. Information was obtained by linking birth certificates, 1990 census data, and death certificates. Children were eligible for the study if they were <5 years of age at any time within the study period and if key study variables were present (99.2% of births). Birth certificates provided information on maternal characteristics including age, race, education, previous live births, use of prenatal care, and residence (in standard metropolitan statistical area). Child characteristics included gender, gestational age, and birth type (singleton/multiple gestation). Neighborhood income was estimated by linking the mother's address at the time of birth to the 1990 census (block group mean per capita income). The study outcome was a fire resulting in at least one fatality (fatal fire event) during the study period, identified from death certificates (coded E880 through E889 in the International Classification of Diseases, 9th rev). We calculated the fatal fire event rate corresponding to each stratum of maternal/child characteristics. We assessed the independent association between each characteristic and the risk of a fatal fire event from a Poisson regression multivariate analysis. During the study period, 1 428 694 children contributed 5 415 213 child years to the cohort: there were 270 deaths from fire (4.99 deaths per 100 000 child years) and 231 fatal fire events. In the multivariate analysis, factors associated with greater than a threefold increase in fatal fire events included maternal education, age, and number of other children. Compared with children whose mothers had a college education, children whose mothers had less than a high school education had 19.4 times (95% confidence interval [CI], 2.6-142.4) an increased risk of a fatal fire event. Children whose mothers had more than two other children had 6.1 times (95% CI, 3.8-9.8) an increased risk of a fatal fire event compared with children whose mothers had no other children. Children of mothers <20 years of age had 3.9 times (95% CI, 2.2-7.1) increased risk of a fatal fire event compared with children whose mothers were >/=30 years old. Although both maternal neighborhood income and race were associated strongly with increased rates of fatal fire events in the univariate analysis, this association did not persist in the multivariate analysis. Other factors that were associated with increased risk of fatal fire events in the multivariate analysis were male gender and having a mother who was unmarried or who had delayed prenatal care. The three factors associated most strongly with fire mortality were combined to create a risk score based on maternal education (>/=16 years, 0 points; 13 to 15 years, 1 point; 12 years, 2 points; <12 years, 3 points); age (>/=30 years, 0 points; 25 to 29 years, 1 point; 20 to 24 years, 2 points; <20 years, 3 points); and number of other children (none, 0 points; one, 1 point; two, 2 points; three or more, 3 points). The lowest-risk group (score <3) included 19% of the population and had 0.19 fatal fire events per 100 000 child years. In contrast, highest-risk children (score >7) comprised 1.5% of the population and had 28.6 fatal fire events per 100 000 child years, 150 times higher than low-risk children. Children with risk scores >5 contributed 26% of child years but experienced 68% of all fatal fire events. If the fatal fire event rate for all children had been equal to that of the low-risk group (risk score <3), then 95% of deaths from


Dye reduction method for estimating bacterial counts in ground beef.
A dye reduction method was developed for estimating total aerobic and/or psychrotrophic bacterial counts in ground beef. The method is based on color changes in indicator disks placed on the meat surface.


Lung development and early origins of childhood respiratory illness.
In the last two decades, 5 cohort studies have been initiated to examine the association of infant respiratory function with genetic and environmental risk factors, as well as with subsequent lower respiratory illness in early childhood. While the current complexity of respiratory function tests in this age group precludes study samples with sufficient power to examine more complex issues, information from these studies has provided an exciting adjunct to that available from the longer cohort studies. Premorbid alterations in airway function or lung development increase the risk of wheezing lower respiratory illnesses during the preschool years and the risk of impaired airway function at 5-6 years of age. In addition, gender differences in airway function and the response to maternal smoking have been observed. Larger collaborative population-based studies are needed to explore the environmental, genetic and immunological mechanisms responsible, but will depend on the development of less invasive tests of airway function appropriate for use in healthy infants.


Studies comparing screen-film mammography and full-field digital mammography in breast cancer screening: updated review.
Full-field digital mammography (FFDM) has several potential benefits as compared with screen-film mammography (SFM) in mammography screening. Digital technology also opens for implementation of advanced applications, including computer-aided detection (CAD) and tomosynthesis. Phantom studies and experimental clinical studies have shown that FFDM is equal or slightly superior to SFM for detection and characterization of mammographic abnormalities. Despite obvious advantages, the conversion to digital mammography has been slower than anticipated, and not only due to higher costs. Until very recently, some countries did not even permit the use of digital mammography in breast cancer screening. The reason for this reluctant attitude was concern about lower spatial resolution and about using soft-copy reading. Furthermore, there was a lack of data supporting improved diagnostic accuracy using FFDM in a screening setting, since two pioneer trials both showed nonsignificantly lower cancer detection rate at FFDM. The 10 studies comparing FFDM and SFM in mammography screening published so far have shown divergent and rather conflicting results. Nevertheless, there is a rapid conversion to digital mammography in breast cancer screening in many western countries. The aim of this article is to give an updated review of these studies, discuss the conflicting findings, and draw some conclusions from the results.


Reconstruction of the popliteal artery after war injury.
During the war against Croatia in 1991-1992, 85 wounded with war injuries of major vessels in the extremities were admitted to the Department of Surgery, Osijek Clinical Hospital. These 85 included 13 (15.3%) wounded with injuries of the popliteal artery. In 12 cases an allograft was used as a substitute conduit. One early thrombosis and two infections occurred. Two amputations had to be performed because of massive soft tissue destruction and infection in the leg tissue. Our experience shows that an allograft is an acceptable choice for popliteal artery reconstruction in a highly contaminated war wound.


Propolis ameliorates restenosis in hypercholesterolemia rabbits with carotid balloon injury by inhibiting lipid accumulation, oxidative stress, and TLR4/NF-κB pathway.
Neointima formation and atherosclerosis are the main complications after the endovascular intervention and vascular surgery, and there are no effective drugs. Propolis is a kind of resin substance produced by honeybees and has numerous health-beneficial effects. In this study, we evaluated the effects of propolis (125 and 250 mg·kg-1 ·day-1 , 6 weeks) on carotid restenosis in hypercholesterolemia rabbits. Propolis significantly ameliorated the degree of carotid restenosis, inhibited neointima hyperplasia, reduced serum lipids profile, and enhanced the anti-oxidative activities in hypercholesterolemia rabbits. Furthermore, propolis reduced the plasma levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α (TNF-α), and inhibited the expression of CD68, TLR4, NF-κB p65, MMP-9, and TNF-α in the carotid arteries. The results indicate that propolis has a protective effect on carotid restenosis in rabbits, which is associated with regulating blood lipids, inhibiting oxidative stress and inflammation, and its anti-inflammatory activity may be related to inhibit TLR4-mediated NF-κB signaling pathway. PRACTICAL APPLICATIONS: Restenosis is a primary challenge in angioplasty and atherosclerotic treatment. Hyperlipidemia can induce inflammation and accelerate the formation of restenosis. Recently, natural products have been widely used to prevent intimal hyperplasia of common cardiovascular diseases. Propolis is currently a popular functional food, but the role of propolis on carotid restenosis after angioplasty and its underlying mechanism remains unclear. This study showed that propolis inhibits the effect of carotid restenosis in hypercholesterolemia rabbits. The results of this study may provide a basis for propolis to prevent and treat vascular restenosis.


Tolerance of Volume Control Noninvasive Ventilation in Subjects With Amyotrophic Lateral Sclerosis.
Noninvasive ventilation (NIV) tolerance has been identified as an independent predictor of survival in amyotrophic lateral sclerosis (ALS). Volume control continuous mandatory ventilation (VC-CMV) NIV has been associated with poor tolerance. The aim of this study was to determine the tolerance of subjects with ALS to VC-CMV NIV. This was a prospective study involving subjects with ALS who were treated with VC-CMV NIV. Respiratory and functional parameters were recorded when the subjects began ventilatory support. NIV tolerance was evaluated after 3 months. Eighty-seven subjects with ALS were included. After 3 months, 80 subjects (92%) remained tolerant of NIV. Tolerant subjects presented greater survival (median 22.0 months, 95% CI 14.78-29.21) than intolerant subjects (median 6.0 months, 95% CI 0.86-11.13) (P = .03). The variables that best predicted NIV tolerance were mechanically assisted cough peak flow (P = .01) and percentage of time spent with SpO2 < 90% at night while on NIV (P = .03) CONCLUSIONS: VC-CMV NIV provides high rates of NIV tolerance in subjects with ALS. Mechanically assisted cough peak flow and percentage of time spent with SpO2 < 90% at night while using NIV are the 2 factors associated with tolerance of VC-CMV NIV in subjects with ALS.


INTRASPECIFIC CHLOROPLAST DNA VARIATION AND BIOGEOGRAPHY OF NORTH AMERICAN LIRIODENDRON L. (MAGNOLIACEAE).
Restriction site variation in chloroplast DNA (cpDNA) was surveyed to analyze population dynamics in Liriodendron tulipifera L., a woody angiosperm found in eastern North America. Two cpDNA haplotypes, differing by the presence or absence of five restriction site changes (nucleotide sequence divergence estimated as approximately 0.15%) are geographically structured; 61 widespread populations possess the "northern" haplotype and three isolated populations of central Florida possess the "southern" haplotype. This geographic break in cpDNA distribution corresponds to patterns of geographic distribution revealed by a previous survey of allozyme variation, with the exception that analyses of allozyme data further divided the populations containing the northern cpDNA haplotype into two groups, a widespread upland group and a coastal intermediate group. Analyses of these two independent data sets together support the hypothesis that L. tulipifera survived the glacial advances of the Pleistocene in two distinct refugia, possibly as different taxa, and the intermediate coastal group was putatively formed from recent hybridizations between these entities.


[Sensitivity to combined metronidazole and penicillin in 227 strains of non-sporulated anaerobic bacteria].
Combined metronidazol-penicillin, used in large amounts corresponding to the selective concentrations in vitro of 25 + 25 IU, may be assumed to be effective in all clinical infections in which one or several anaerobes are implicated. The experiments carried out demonstrate that this is valid for all categories of Grampositive or Gramnegative non-sporulate anaerobes. The antibiotic concentrations used are well tolerated by the human organism.


Visual defects in white-tailed deer from Michigan six case reports.
Six cases of unrelated visual defects in free-ranging white-tailed deer (Odocoileus virginianus) from Michigan are described. Two were congenital, two were of infectious etiology, one from central nervous neoplasia, and one from degenerative changes in lenses of both eyes.


Modified Glasgow Prognostic Score 2 as a Prognostic Marker in Patients With Metastatic Urothelial Carcinoma.
Predicting the prognosis of metastatic urothelial carcinoma (mUC) patients is needed for clinical decisions. We examined the value of a modified Glasgow prognostic score (mGPS) as a predictive marker for mUC patients. In a multicenter study, 68 mUC patients received short hydration gemcitabine/cisplatin (shGC) and 74 received pembrolizumab (PEM). Patients were allocated according to mGPS. Progression-free (PFS) and cancer-specific (CSS) survival were examined. Higher mGPS reflected poorer PFS and CSS in shGC (p=0.03, p<0.0001, respectively) and PEM (p=0.02, p<0.001, respectively) patients. PFS for the high mGPS group was longer than that of the low mGPS group in the two cohorts (p <0.0001 for both), with similar CSS results (p<0.0001 and p<0.001, respectively). Multivariate analyses revealed high mGPS was a risk factor for poor CSS in both cohorts (HR=3.55, p<0.001, and HR=2.21, p<0.01, respectively). In the mUC patients receiving shGC or PEM, mGPS was a predictive prognostic marker.


Simultaneous induction of antigen-specific IgA helper T cells and IgG suppressor T cells in the murine Peyer's patch after protein feeding.
The effects of feeding the dietary protein antigen, ovalbumin (OVA), on OVA-specific IgG and IgA immune responses involving Peyer's patches (PP) and mesenteric lymph nodes (MLN) were examined. Mice were administered soluble OVA by gastric intubation. One to 3 days later, PP, MLN, or spleen cells from these donor mice were adoptively transferred into normal syngeneic recipients. After two subsequent immunizations, spleens from the recipient mice were assayed for IgA and IgG anti-OVA plaque-forming cell (PFC) responses. None of the tissues from normal (unfed) mice had the inherent ability to alter recipients' IgG or IgA PFC responses. Within 1 day of OVA feeding, however, cells were generated in the PP that could augment recipients' IgA anti-OVA PFC responses and suppress IgG PFC responses. Three days after OVA feeding, these cells were present in MLN as well, and whereas the IgG suppressor cell also appeared to migrate to spleen, the IgA helper cell did not. The cells mediating antigen-specific IgG suppression and IgA help were both T cells but could be distinguished by surface phenotype. We therefore conclude that protein feeding induces differential, isotype-specific immunoregulation in gut-associated lymphoid tissues, part of which is mediated by an antigen-specific IgA helper T cell.


Enantioselective construction of ortho-substituted benzylic quaternary centers using a phenanthroline-Pd catalyst.
A method for Pd-catalyzed asymmetric conjugate addition of ortho-substituted arylboronic acids to cyclic enones was developed. The addition of various ortho-substituted arylboronic acid to β-substituted cyclic enones, via catalysis with a chiral phenanthroline-Pd complex, formed cyclic ketone products bearing ortho-substituted benzylic all-carbon quaternary centers with good yields and high enantioselectivity.


Clinical imperative versus economic consequence: exploring the cost burden and opportunities in the care of patients with sepsis.
Balancing clinical quality, safety, and cost is not new to health care leaders; however, the current environment of public transparency coupled with unprecedented economic challenges has created a sense of urgency to this triathlon-like balance. The implementation of clinically proven, life-saving therapy in the care of patients with sepsis is one of the highest financial burdens incurred by acute care facilities; however, the absence of that care is known to be the leading cause of death in noncoronary intensive care units and the 10th leading cause of death worldwide. Can we afford to save these lives? Through root-cost analysis of intensive care unit-care in conjunction with population management strategies, the synergy of bundled therapies in driving positive clinical outcomes can be replicated in the achievement of an outcome bundle including quality improvement, safety enhancement, and financial stewardship.


Persistence of pneumococcal antibodies after immunization in patients with systemic lupus erythematosus.
Antibody levels to 12 different pneumococcal capsular polysaccharides as well as the combined mean antibody level were measured in 19 patients with systemic lupus erythematosus (SLE) at 1, 2 and 3 years after immunization with a polyvalent pneumococcal vaccine and compared to 5 normal control subjects immunized at the same time. The mean levels in the 19 SLE patients were lower in all 3 years but the difference reached significance only in Year 1. At 3 years, 8 of the 19 SLE patients had levels below that considered to be protective and one such patient developed a pneumococcal pneumonia.


Threats to group value, domain-specific self-esteem and intergroup discrimination amongst minimal and national groups.
The research reported in this investigation sought to examine the self-esteem hypothesis (SEH) using measures of domain-specific and public collective self-esteem (CSE). Two studies were conducted. Each tested both propositions of the SEH. The first study revealed that minimal group members (a) experienced an increase in that domain of self-esteem judged to be relatively more important to the in-group, following the display of in-group favouritism and (b) that minimal group members with low public CSE (and who thus believed that the in-group was negatively evaluated by the out-group) showed enhanced levels of in-group favouritism. The second study, which utilized the members of real social categories (i.e. New Zealanders and Australians) and negative outcome allocations (i.e. white noise) revealed identical findings. The theoretical implications of these results are discussed.


The HDAC10 instructs macrophage M2 program via deacetylation of STAT3 and promotes allergic airway inflammation.
Background: Perturbation of macrophage homeostasis is one of the key mechanisms of airway inflammation in asthma. However, the exact mechanisms remain poorly understood. Objectives: We sought to examine the role of histone deacetylase (HDAC) 10 as an epigenetic regulator that governs macrophage M2 program and promotes airway inflammation in asthma, and to elucidate the underlying mechanisms. Methods: Peripheral blood and airway biopsies were obtained from healthy individuals and asthmatic patients. Asthma was induced by exposure to allergen in mice with myeloid-specific deletion of Hdac10 (Hdac10fl/fl-LysMCre) mice. HDAC10 inhibitor Salvianolic acid B (SAB), STAT3 selective agonist Colivelin, and the specific PI3K/Akt activator 1,3-Dicaffeoylquinic acid (DA) were also used in asthmatic mice. For cell studies, THP1 cells, primary mouse bone marrow derived macrophage (BMDMs) were used and related signaling pathways was investigated. Results: HDAC10 expression was highly expressed by macrophages and promoted M2 macrophage activation and airway inflammation in asthmatic patients and mice. Hdac10fl/fl-LysMCre mice were protected from airway inflammation in experimental asthma model. Hdac10 deficiency significantly attenuated STAT3 expression and decreased M2 macrophage polarization following allergen exposure. Mechanistically, HDAC10 directly binds STAT3 for deacetylation in macrophages, by which it promotes STAT3 expression and activates the macrophage M2 program. Importantly, we identified SAB as a HDAC10 inhibitor that had protective effects against airway inflammation in mice. Conclusions: Our results revealed that HDAC10-STAT3 interaction governs macrophage polarization to promote airway inflammation in asthma, implicating HDAC10 as a therapeutic target.


[Physiology of ovarian function].
The ovarian function including follicular maturation, ovulation and corpus luteum formation is regulated by a complex control system composed of hypothalamus, pituitary and the ovary itself. These organs communicate via positive and negative feedback loops and can be considered as a functional entity. Special neurons in the hypothalamus produce gonadotropin-releasing hormone (GnRH) being delivered to the anterior pituitary lobe by the pituitary portal vessels. GnRH binds to specific receptors inducing synthesis and release of the gonadotropins FSH and LH into the circulation. After binding to their specific receptors at the ovary FSH and LH induce follicular maturation, ovulation and corpus luteum formation. The ovary responds to gonadotropin stimulation in dual fashion: secretion of sexsteroids and the liberation of a fertilizable oocyte. In addition the ovary is also able to secrete peptide-hormones such as inhibin and activin. Sexsteroids and inhibin modulate the pulsatile secretion of GnRH and gonadotropins. Cooperation of theca- and granulosa cells at the ovarian level and the corpus luteum formation are described and the significance of growth factors and cytocines is emphasized. The effects of estradiol and progesterone are highlighted by the morphological response of the endometrium. The ovary is actively involved in maintaining cyclicity, as reflected by the processes of follicular growth, follicle rupture and formation of the corpus luteum with the dramatic morphological changes involved.


Transplanted sympathetic neurons from old rats survive in the anterior eye chamber: a histochemical and electron microscopic study.
The purpose of this study was to investigate the viability and ultrastructural characteristics of intraocular superior cervical ganglion (SCG) grafts from young (3 months), aged (24 months) and very old (36 months) rats after short-term (1 month) grafting. The formaldehyde-induced fluorescence (FIF) technique for histochemical demonstration of catecholamines was used to indicate the functionality of transplanted neurons. Ultrastructural changes in grafts were demonstrated by electron microscopy. Four weeks after transplantation, catecholamine histofluorescence in young transplants was almost as strong as in the intact ganglia, while aged and very old grafts showed decreased fluorescence and contained a marked accumulation of autofluorescent lipopigment bodies. Catecholamine histofluorescence showed a decrease in neuronal density of 47%, 59% and 68% in young, aged and very old grafted ganglia, respectively. The shape of most of the transplanted neurons did not differ from that in the intact ganglia, but the average diameter of neurons was decreased after grafting. In electron microscopy, both neurons with normal in vivo fine structure and neurons showing some abnormal cytological alterations were seen in each age group of the transplants. The most prominent feature after grafting was the accumulation of different types of lipopigment bodies in the perikarya of neurons. the organization of the rough endoplasmic reticulum was more irregular in transplanted neurons than in intact neurons. In addition, the amount of neurofilament aggregates increased and some mitochondria were swollen in neurons after transplantation. These results suggest that young sympathetic ganglion tissue survives rather well after transplantation into the anterior eye chamber, while in the aged sympathetic ganglion implants the survival rate is poorer. However, aged and very old SCG grafts were shown to contain and continue to produce noradrenaline, indicating that sympathetic neurons maintain their plasticity and regenerative ability in advanced age. Catecholamine histofluorescence and fine structural changes in the cell structure of grafted sympathetic neurons may indicate an accelerated aging process induced by the transplantation procedure.


Open-wound treatment for gunshot to the brain.
The authors report a case of a gunshot wound to the brain in a 2.5-year-old girl. To treat the uncontrollably elevated intracranial pressure, the patient underwent bilateral decompressive craniectomy and experimental open-wound treatment. She recovered to a good functional level.


Cataracts and phacoemulsification in the Siberian Husky: A retrospective and multicentric study (2008-2018).
To compare cataract characteristics and complications related to cataracts and phacoemulsification in the Siberian Husky (Huskies) versus other canine breeds (non-Huskies). A total of 50 Huskies (92 eyes) and 96 non-Huskies (182 eyes) were evaluated. Medical records of Huskies (at four university veterinary hospitals, 2008-2018) and non-Huskies (Colorado State University, 2017-2018) diagnosed with cataracts were reviewed. Age of dog, cataract stage at presentation, and pre- and post-operative complications were recorded and analyzed. Mean (±standard deviation) age at presentation was significantly lower in Huskies (3.5 ± 3.3 years) compared to non-Huskies (9.5 ± 2.9 years) (p < .0001). Huskies more commonly presented with hereditary cataracts than non-Huskies (84% versus 52%) and a significantly higher percentage of non-Huskies presented with diabetic cataracts than Huskies (48% versus 16%; p = .0001). Cataract stage at presentation did not differ between Huskies and non-Huskies. Phacoemulsification was performed in 40% (20 out of 50 dogs, 39 out of 92 eyes) of Huskies and 42% (40 out of 96 dogs, 74 out of 182 eyes) of non-Huskies. Pre-operative and post-operative retinal detachment were more common in Huskies than non-Huskies (13% versus 2% and 10% versus 1%, respectively) but the difference was not significant. Other post-operative complications occurred with similar frequency in both groups (p ≥ .17). Huskies evaluated for cataracts were younger and less likely to present with diabetic cataracts than other canine breeds and, although not statistically significant, had a clinically important increased risk of retinal detachment pre- and post-phacoemulsification.


Risk stratification and outcomes of intracranial hemorrhage in patients with immune thrombocytopenia under 60 years of age.
Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/μL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.


An improved method of examining adult Onchocerca volvulus worms.
Adult Onchocerca volvulus worms were extracted from alcohol-fixed nodules by collagenese digestion. The worms were stained in Mayer's haematoxylin and brought up into glycerol. In this viscous fluid the stained and cleared worms could be unravelled in sequential lengths of 4-6 cm and mounted in glycerol on slides for longitudinal examination of their structure. The worm lengths were then cut into small pieces, 0.5 cm long, which were implanted sequentially into slits in a brick-shaped block of formalin-fixed calf's brain (white matter) also in glycerol. The brain blocks were then processed in paraffin wax and cut as 6 microns histological sections, enabling transverse sections of the worm, stained as required, to be examined in sequential order.


Isolation, preliminary characterization, and interferon antagonistic effect of a mammalian lectin-like substance.
We have isolated from mouse costal cartilage a tissue antagonist of interferon (TAI) which accelerates the decay of an established antiviral state. The effect is reminiscent of substances previously isolated from the basement membrane of human amnion. Since we have recently shown that phytohemagglutinin can mimic the biological effect of TAI, we have explored the possibility that TAI could be an animal lectin-like material. First, TAI agglutinates mouse cells; second, this cell agglutination is inhibited by some sugars. Preliminary characterization indicates that the active molecule is a protein. After Sephadex G-100 gel filtration, TAI is found in a peak of 150,000 molecular weight. When purified by isoelectric focusing, this peak shows maximal activities corresponding to an isoelectric point of pH 8.8 TAI binds to polysaccharide residues of the cell membrane which could be its primary site of action, comparable to phytohemagglutinin.


Sodium removal and peritoneal dialysis modalities: no differences with optimal prescription of icodextrin.
Continuous ambulatory peritoneal dialysis (CAPD) has been considered as a more efficient modality for sodium removal than automated peritoneal dialysis (APD), due to the longer dwell times and the sodium sieving phenomenon. However, because studies regarding sodium removal in peritoneal dialysis (PD) report rather controversial results and carry various methodological flaws, it remains uncertain whether they offer enough significant information regarding PD prescription and therapy. The aim of the present observational cross-sectional study was to evaluate the impact of the optimal prescription of CAPD and APD, regarding solute clearances and daily ultrafiltrate, on daily sodium removal. Forty-six (46) patients aged 52.3 ± 14 years were studied. Twenty-six (26) patients were subjected to CAPD, and 20 patients were subjected to APD. Ten (10) patients per group were prescribed icodextrin for the long dwell to achieve optimal adequacy and ultrafiltration (UF) targets. CAPD patients removed a higher, albeit not statistically significant, daily amount of sodium (131.7 ± 98.2 mmol) compared with APD patients (79.4 ± 129.2 mmol). Their Kt/V urea was lower (1.48 ± 0.3 vs. 2.17 ± 0.33, P < 0.05), and there were no differences on daily UF (1119 ± 533 vs. 1005 ± 517 mL). In both groups, icodextrin use for the long dwell resulted in equal sodium removal with that of patients not prescribed icodextrin. Our results, derived from an unselected PD population, indicate that although classic CAPD may be more efficient for sodium removal than APD, the use of icodextrin as an adjuvant for higher daily UF not only increases solute clearance but also removes more sodium for both modalities. In addition, calculations of sodium removal in PD do not seem to benefit the everyday clinical practice, provided that PD patients can achieve the adequacy targets and present optimal daily UF without signs of volume overload.


Circadian clock control of tRNA synthetases in Neurospora crassa.
Background: In Neurospora crassa, the circadian clock controls rhythmic mRNA translation initiation through regulation of the eIF2α kinase CPC-3 (the homolog of yeast and mammalian GCN2). Active CPC-3 phosphorylates and inactivates eIF2α, leading to higher phosphorylated eIF2α (P-eIF2α) levels and reduced translation initiation during the subjective day. This daytime activation of CPC-3 is driven by its binding to uncharged tRNA, and uncharged tRNA levels peak during the day under control of the circadian clock. The daily rhythm in uncharged tRNA levels could arise from rhythmic amino acid levels or aminoacyl-tRNA synthetase (aaRSs) levels. Methods: To determine if and how the clock potentially controls rhythms in aspartyl-tRNA synthetase (AspRS) and glutaminyl-tRNA synthetase (GlnRS), both observed to be rhythmic in circadian genomic datasets, transcriptional and translational fusions to luciferase were generated. These luciferase reporter fusions were examined in wild type (WT), clock mutant Δ frq, and clock-controlled transcription factor deletion strains. Results: Translational and transcriptional fusions of AspRS and GlnRS to luciferase confirmed that their protein levels are clock-controlled with peak levels at night. Moreover, clock-controlled transcription factors NCU00275 and ADV-1 drive robust rhythmic protein expression of AspRS and GlnRS, respectively. Conclusions: These data support a model whereby coordinate clock control of select aaRSs drives rhythms in uncharged tRNAs, leading to rhythmic CPC-3 activation, and rhythms in translation of specific mRNAs.


Toxin-antitoxins and bacterial virulence.
Bacterial virulence relies on a delicate balance of signals interchanged between the invading microbe and the host. This communication has been extensively perceived as a battle involving harmful molecules produced by the pathogen and host defenses. In this review, we focus on a largely unexplored element of this dialogue, as are toxin-antitoxin (TA) systems of the pathogen. TA systems are reported to respond to stresses that are also found in the host and, as a consequence, could modulate the physiology of the intruder microbe. This view is consistent with recent studies that demonstrate a contribution of distinct TA systems to virulence since their absence alters the course of the infection. TA loci are stress response modules that, therefore, could readjust pathogen metabolism to favor the generation of slow-growing or quiescent cells 'before' host defenses irreversibly block essential pathogen activities. Some toxins of these TA modules have been proposed as potential weapons used by the pathogen to act on host targets. We discuss all these aspects based on studies that support some TA modules as important regulators in the pathogen-host interface.


Preparative Purification of Linarin Extracts from Dendranthema indicum Flowers and Evaluation of Its Antihypertensive Effect.
Background. Preliminary research showed that linarin (LIN) might have a relationship with the antihypertensive effect of Dendranthema indicum flowers. However, the preparative method for LIN enriched extract from Dendranthema indicum flowers was not clear and its antihypertensive effect was not confirmed. In this study, we designed a series of experiments to develop an efficient method for purification of LIN extracts and confirm the possibility of LIN extracts to be an antihypertensive drug. Materials and Methods. HPLC-VWD/DAD were used in the process of developing purification method. The antihypertensive effect of LIN extracts was tested by CODA Mouse & Rat Tail-Cuff Blood Pressure System; western blot and biochemical analysis were used to investigate mechanism and toxicity. Results. The content and recovery of LIN reached 55.68 ± 2.08% and 66.65 ± 1.73%, respectively, through solid-liquid extraction. The composition of product was stable through the analysis of fingerprint. Chronic administration of LIN extracts reduced blood pressure obviously which had a relationship with the inhibition of renin-angiotensin system (RAS) in kidney and the function indexes of kidney and liver had no variations. Conclusions. The preparation method was simple, low-cost, and stable, and it was fit for industrial application. The LIN prepared by this method had the potential to be an antihypertensive drug.